International Study of Subsequent Colorectal Cancer Among Survivors of Childhood, Adolescent, and Young Adult Cancers (I-SCRY)

项目摘要/摘要 儿童期、青春期和青壮年(Aya)癌症的幸存者有更高的后续风险 与发病率和过早死亡有关的恶性肿瘤。新出现的证据 建议与腹部或盆腔放疗相关的结直肠癌(CRC)用于治疗 儿童期或阿亚癌就是这样一种肿瘤。早期研究表明，其他治疗暴露包括 顺铂和烷化剂治疗也可能与结直肠癌风险相关，并可能与放射治疗相互作用 使风险显著升高。了解接触这些疗法的年龄是否会改变风险 有限的。此外，与治疗相关的结直肠癌的预后尚不清楚。这些知识上的差距是 由于任何单一队列中的CRC数量有限，缺乏关于原发癌症的详细信息 一些队列的治疗，队列的相对年轻年龄，以及现有队列的重点是 儿童癌症幸存者或特定青年癌症幸存者。 我们建议利用八个国际儿童和癌症幸存者的独特资源 一群人。我们将汇集51,309名幸存者的个人参与者数据，其中298名患有CRC，并进行中位随访 在初级癌症诊断后13到26年的范围内进行研究，以全面检查风险 继发复发性癌的因素和死亡率。这几乎是已知任何一种类型的CRC数量的四倍 有详细治疗数据的儿童期或阿亚期队列。因此，童年和阿雅的结合 癌症幸存者进入单一队列是新颖的，并给予儿科和AYA的常见治疗方法 癌症，将使我们能够解决这些问题，有能力评估年龄在暴露时的作用。 该项目的主要目的是评估儿童与癌症治疗之间的联系。 (腹部和/或盆腔辐射场和剂量，以及化疗暴露，包括累积 烷化剂、蒽环类药物、铂剂的剂量)在一项大型、多队列的国际研究中对结直肠癌风险的影响 幸存者人口。次要目标将侧重于扩大对儿童权利公约负担的评估 在童年和阿雅癌症的幸存者。这包括估计和比较结直肠癌的发病率。 儿童和Aya癌症幸存者与普通人群中结直肠癌发病率的关系 儿童和癌症幸存者经结直肠癌诊断后的死亡率特征，并与 这是在普通人群中进行新的CRC诊断后观察到的。 这项工作的结果可能有助于完善筛查指南和策略 防止CRC。此外，为了实现我们的目标，我们将建立一种资源，可用于 未来由研究者发起的研究。

PROJECT SUMMARY / ABSTRACT Survivors of childhood, adolescent, and young adult (AYA) cancer have an elevated risk of subsequent malignant neoplasms which are associated with morbidity and premature mortality. Emerging evidence suggests that colorectal cancer (CRC), associated with abdominal or pelvic radiotherapy used to treat the childhood or AYA cancer, is one such neoplasm. Early studies indicate other treatment exposures, including cisplatin and alkylator therapy, may also be associated with CRC risk and may interact with the radiotherapy to confer a markedly elevated risk. Knowledge of whether age at exposure to these therapies might modify risk is limited. Further, prognosis after a treatment-related CRC is not well-understood. These gaps in knowledge are due to the limited number of CRCs in any single cohort, lack of detailed information on primary cancer treatments for some cohorts, the relatively young age of cohorts, and the focus of existing cohorts on either childhood cancer survivors or on survivors of specific young adult cancers. We propose to leverage the unique resources of eight international childhood and AYA cancer survivor cohorts. We will pool individual participant data on 51,309 survivors, 298 with CRC, and with median follow-up across studies ranging from 13 to 26 years after primary cancer diagnosis, to comprehensively examine risk factors of, and mortality after, subsequent CRCs. This is almost four-fold the number of CRCs in any known childhood or AYA cohort with detailed treatment data available. Thus, the combination of childhood and AYA cancer survivors into a single cohort is novel and given common treatment approaches to pediatric and AYA cancer, will enable us to address these questions with the ability to assess the role of age at exposure. The primary aim of this project is to evaluate the association of childhood and AYA cancer therapy (abdominal and/or pelvic radiation fields and dose, as well as chemotherapy exposures including cumulative doses of alkylating agents, anthracyclines, platinating agents) on CRC risk in a large, multi-cohort, international survivor population. Secondary aims will focus on conducting an expanded assessment of the burden of CRC in childhood and AYA cancer survivors. This includes estimating and comparing the incidence of CRC in childhood and AYA cancer survivors to the incidence of CRC in the general population, as well as characterizing mortality following a CRC diagnosis in childhood and AYA cancer survivors and comparing it to that observed following a de novo CRC diagnosis in the general population. The results from this work have the potential to help refine screening guidelines and strategies for preventing CRC. In addition, in achieving our aims, we will establish a resource that may be leveraged for future investigator-initiated research.